A bacteria that causes melioidosis has been found in the soil and water for the first time in the continental United States, officials from the Centers for Disease Control and Prevention (CDC) announced today.
The gram-negative bacteria, Burkholderia pseudomallei or B. pseudomallei, was found on the property of a Mississippi man who had come down with the disease, melioidosis.
It is unclear how long the bacteria have been in the environment and where else it might be found in the U.S.; however, modeling suggests that the environmental conditions found in the Gulf Coast states are conducive to the growth of B. pseudomallei. CDC is alerting clinicians throughout the country of this discovery through a national health advisory, reminding them to be aware of the signs and symptoms of melioidosis and to consider melioidosis in patients that present with symptoms of the disease.
Two unrelated individuals living in close geographic proximity in the Gulf Coast region of the southern United States became sick with melioidosis two years apart—in 2020 and 2022— prompting state health officials and CDC to take samples and test household products, soil, and water in and around both patients’ homes, with permission. Three of the samples taken from soil and puddle water in 2022 tested positive at CDC for B. pseudomallei, indicating bacteria from the environment was the likely source of infection for both individuals and has been present in the area since at least 2020.
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The bacteria that cause melioidosis usually enter the body through inhalation of soil dust or water droplets, contact with contaminated soil through breaks in the skin, or by ingestion of contaminated water. Person-to-person transmission is very rare, but can occur through contact with blood or body fluids of an infected person. Laboratory-acquired infections are also rare, but can occur, especially if procedures produce aerosols.
The bacteria can infect the skin or lungs or can spread throughout the body. The symptoms that a person might develop depend on the location of infection. Some people might not develop any symptoms. Localized infections, such as skin wounds, are characterized by pain or swelling at a particular site, fever, ulceration, or abscess. Symptoms of lung infection include cough, chest pain, fever, headache, or decreased appetite. If the bacteria enter the blood, symptoms include fever, headache, respiratory difficulties, abdominal pain or discomfort, joint pain, or disorientation. If the bacteria spread throughout the body (disseminated infection), symptoms include fever, weight loss, stomach or chest pain, muscle or joint pain, headache, and seizures.
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Among the average of 12 melioidosis cases diagnosed in the U.S. each year, most have occurred in people with recent travel to a country where B. pseudomallei is endemic, including certain regions of Australia, Thailand, and Central and South America. U.S. physicians should consider melioidosis even in patients who haven’t traveled to other countries, the CDC said in the health alert.
Individuals living in the Gulf Coast of Mississippi and who have health conditions that may put them at higher risk—such as diabetes, chronic kidney disease, chronic lung disease, or excessive alcohol use— should take precautions to protect themselves:
- Avoid contact with soil or muddy water, particularly after heavy rains, and protect open wounds with waterproof dressings.
- Wear waterproof boots when gardening, doing yard work, or doing agricultural work, which can prevent infection through the feet and lower legs—particularly after flooding or storms.
- Wear gloves to protect the hands when working directly with soil.
Worldwide, melioidosis is fatal in 10 – 50% of those infected. B. pseudomallei has historically been found in tropical and sub-tropical areas such as South and Southeast Asia, northern Australia, and parts of Central and South America and Puerto Rico. Given the very small number of cases of melioidosis identified historically in the U.S., CDC believes the risk of melioidosis for the general population continues to be very low.
Due to a high associated mortality rate, wide availability in the environment in endemic areas, intrinsic resistance to many countermeasures (antibiotics) and the potential for aerosol spread, B. pseudomallei is considered to have potential as a bioterrorism agent and is designated a Tier 1 Agent on the HHS and USDA Select Agents and Toxins list.
Source: Centers for Disease Control and Prevention
Nature Reviews Disease Primers
Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host’s immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival.
Melioidosis: Evolving Concepts in Epidemiology, Pathogenesis, and Treatment
Seminars in Respiratory and Critical Care Medicine
Infection with Burkholderia pseudomallei can result in asymptomatic seroconversion, a single skin lesion that may or may not heal spontaneously, a pneumonia which can be subacute or chronic and mimic tuberculosis or rapidly progressive resulting in fatal overwhelming sepsis. Latency with subsequent activation of disease is well recognized, but very uncommon. Melioidosis also has a myriad of other clinical presentations and diagnosis is often delayed because of this and because of difficulties with laboratory diagnosis and lack of recognition outside melioidosis-endemic regions. The perception of B. pseudomallei as a top tier biothreat agent has driven large funding for research, yet resources for diagnosis and therapy of melioidosis in many endemic locations remain extremely limited, with mortality as high as 50% in comparison to around 10% in regions where state-of-the-art intensive care therapy for sepsis is available.
While biothreat research is directed toward potential aerosol exposure to B. pseudomallei, the overall proportion of melioidosis cases resulting from inhalation rather than from percutaneous inoculation remains entirely uncertain, although the epidemiology supports a shift to inhalation during severe weather events such as cyclones and typhoons. What makes B. pseudomallei such a dangerous organism for patients with diabetes and other selective risk factors remains unclear, but microbial genome-wide association studies linking clinical aspects of melioidosis cases to nonubiquitous or polymorphic B. pseudomallei genes or genomic islands are beginning to uncover specific virulence signatures. Finally, what also remains uncertain is the global phylogeography of B. pseudomallei and whether melioidosis is spreading beyond historical locations or is just being unmasked in Africa and the Americas by better recognition and increased surveillance.
In Silico Designing of a Multi-Epitope Vaccine Against Burkholderia Pseudomallei: Reverse Vaccinology and Immunoinformatics
Journal of Genetic Engineering and Biotechnology
In this study, in silico approach was applied to design a multi-epitope subunit vaccine peptide consisting of linear B-cell and T-cell epitopes of proteins considered to be potential novel vaccine candidates.
Development of Melioidosis Subunit Vaccines Using an Enzymatically Inactive Burkholderia pseudomallei AhpC
Infection and Immunity
Previous preclinical vaccine studies have explored the use of live attenuated bacteria, outer membrane vesicles, nanoparticle platforms, glycoconjugates, and multivalent subunit formulations with varied success. Research in our lab focuses on the development of glycoconjugate-based subunit vaccines, an approach that is generally considered safe and utilizes a defined set of antigens, which allows for the determination of antigen-specific correlates of immunity. In this study, researchers evaluated the immunogenicity and protective capacity of B. pseudomallei alkyl hydroperoxide reductase subunit C (AhpC) in combination with CPS-CRM197. AhpC is a peroxiredoxin involved in oxidative stress reduction and is a potential protective antigen. The findings demonstrate AhpC is a potent activator of cellular and humoral immune responses and may be a promising candidate to include in future melioidosis subunit vaccines.
Evaluation of Antigen-Detecting and Antibody-Detecting Diagnostic Test Combinations for Diagnosing Melioidosis
PLOS Neglected Tropical Diseases
Melioidosis is an infection caused by the Gram-negative bacterium Burkholderia pseudomallei. There are currently no commercially available and reliable point-of-care diagnostic tests for melioidosis. We previously demonstrated that a prototype lateral flow immunoassay (LFI) developed to detect B. pseudomallei capsular polysaccharide (CPS) had limited sensitivity (31.3%) but high specificity (98.8%) for diagnosing melioidosis among patients presenting with community-acquired infection or sepsis in northeast Thailand. Here, we evaluated combinations of the CPS-LFI and enzyme-linked immunosorbent assays (ELISA) that detect antibodies against hemolysin co-regulated protein (Hcp1) or O-polysaccharide (OPS). When used in combination, results were considered positive if either test was positive. We selected ELISA cut-offs corresponding to a specificity of 95%. Our results demonstrated that a combination of antigen-detection (CPS-LFI) and antibody-detection (Hcp1-ELISA or OPS-ELISA) tests increased the sensitivity for diagnosis of melioidosis (68% or 63%, respectively) over any single test, while maintaining high specificity (95%). In case patients, positivity of the CPS-LFI was associated with a short duration of symptoms, severe infections (as measured by an organ failure assessment score), bacteraemia and mortality outcome, while positivity of Hcp1-ELISA was associated with a long duration of symptoms, non-bacteraemia and survival outcome. Based on our findings, we propose that point-of-care melioidosis diagnostic tests using combinations of antigen- and antibody-detection should be further developed and evaluated.